Direct allylation

The direct allylation of 2-phenylpropanal proceeds with much lower selectivity [2-propenylmagnesium bromide 73 27 allyltrimethylsilane/titanium(IV) chloride 67 33]27. 

A somewhat related microwave-promoted 5 -0-allylation of thymidine has been described by the Zerrouki group (Scheme 6.108) [215], While the classical method for the preparation of 5 -0-allylthymidine required various protection steps (four synthetic steps in total), the authors attempted the direct allylation of thymidine under basic conditions. Employing sodium hydride as a base at room temperature in N,N-dimethylformamide resulted in the formation of per-allylated compounds along with the desired monoallylated product (75% yield). The best result was achieved when both the deprotonation with sodium hydride (1.15 equivalents) and the subsequent allylation (1.2 equivalents of allyl bromide) were conducted under... 

Imidazoles/benzimidazoles and chiral carbinamines are of particular importance [73, 74], Recently, Leighton et al. developed a method for enantioselec-tive imidazole directed allylation of aldimines and ketimines [75] with an analogue of 31. 

Allylic acetates are usually prepared by esterification from allylic alcohols. However, the corresponding alcohols are often only accessible by the fairly expensive hydride reduction of carbonyl compounds. Consequently, direct allylic functionalization of easily available olefins has been intensively investigated. Most of these reactions involve peroxides or a variety of metal salts.However, serious drawbacks of these reactions, (e.g. toxicity of some metals, stoichiometric reaction conditions, or nongenerality) may be responsible for their infrequent use for the construction of allylic alcohols or acetates. 

More recently, Srivastava and Nicholas discovered the direct allylic amination with nitroaromatics 38 as effective aminating agents under catalysis by the inexpensive [CpFe(CO)2]2 (Scheme 3.38) [134],... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

Scheme 18. o-DPPB-directed allylic substitution with organocopper reagents. 

Direct allylation of rhodanine 49 (Scheme 13) under Pd(0)-catalysis with cinnamyl ethyl carbonate affords the /V-allylated compound 50. However, allylation with cinnamyl bromide and a base is not regioselective, producing a mixture of 50 and sulfide 51. Sulfide 51 isomerizes to 50 under palladium catalysis (N > S), thus indicating that Pd(0)-catalyzed allylation of 49 is thermodynamically controlled (93T1465). 

The reaction of 153 with the stannylated acetate 162 (Scheme 36) shows the directing effect of the Bu3Sn group. Both direct allylation and rearrangement of 164 give 163. Tin elimination from 163b (step c) results in the incorporation of a branched 2-butenyl chain in 165 (92ACS1215). 

We have studied the direct allylation of uracil 190, thymine 191, and 6-methyluracil 192 (Scheme 43) under Pd(0) catalysis and forcing conditions (93T1457). The results are summarized in Table V. Uracil and thymine... 

The synthetic methods for the preparation of allyl amines can be divided into several types of reactions [1]. In the present chaptgr, the focus will be on the formation of allyl amines by reaction of substrates having an allylic bond which can be broken. Two approaches will be covered and these are outlined in Scheme 1 the first method (a) is the synthesis of allyl amines by nucleophilic allylic substitution of compounds having an allyl functionality the second method (b) is the direct allylic amination of simple alkenes. 

The reaction type (a) in Scheme 1 for the allylic amination reaction uses substrates which have an allylic C-X (X = heteroatom, halide) bond and is mainly nucleophilic amination of functionalized alkenes, whereas reaction type (b) is a direct allylic amination of an alkene, based on electrophilic amination of nonfunctionalized alkenes and involves a cleavage of a C-H bond. 

Sharpless et al. and Muccigrosso et al. were probably the first to perform the direct allylic amination of nonfunctionalized alkenes in the presence of a metal complex [60]. The complex used for the allylic amination was the molibdooscaziridine 109 prepared by reaction of the molybdenum dioxo complex 107 and phenyl hydroxy-lamine 108 (Eq. (25)). 

A rhenium catalyst is quite valuable for the direct allylation of cr-aryl-substituted propargyl alcohols with 10 (Equation (58)).220 Benzyl alcohols are efficiently allylated with allylchlorodimethylsilane under catalysis by InCl3.221... 

Compared with the direct allylation of carbonyl groups, little has been reported on the selective conjugate allylation of enones. Allylic tantalum species, generated by the Sn-Ta exchange, is the choice of tools for performing conjugate addition of sterically hindered allylic groups (Equation (43)).140... 

The direct allylation of aromatic compounds with allylic chlorides is achieved in the presence of a catalytic amount of indium metal. According to the authors, indium is considered to act as a Lewis acid (Equation (101)).399 Trialkylindiums react with acid chlorides to give ketones. When trialkylindiums are treated with air prior to the reaction with acid chlorides, esters are formed (Scheme 121).400 The reaction of cyclopentadienylindium(i) with aldehydes in aqueous media gives mixtures of the isomeric coupling products (Equation (102)).401... 

The acceleration of the 3-aza-Cope rearrangement of A-allylenamines through formation of a cationic quaternary nitrogen center (enammonium salt) has obvious advantages. However, direct allylation of enamines in order to form the enammonium ions is unsatisfactory, and difficult. Moreover, the rearrangement-hydrolysis product is often contaminated by the C-allylated product when an unsymmetrical allyl halide is employed... 

Attempts have been made to exploit the possibility of direct allylic oxidation of codeine with chromic acid,(253) Mn02,(254) and SeOz plus t-butyl hydroperoxide(255) to the corresponding 14-OH derivative, but each approach gave a low yield. Schwartz and Wallace 255 achieved a six-step transformation of codeine to a noroxycodone (52%) and noroxymorphone (43%) according to Scheme 2.20. Oxidation of the carbamate of norcodeine gave 166 (R = H), which was converted to the dienol acetate, 167. Subjection of this to... 

Transition metal (such as Pd, Ir, Mo and W)-catalyzed asymmetric allylic substitutions with various nucleophiles are widely employed in organic synthesis and played an important role in the area of asymmetric C-C bond formation. Trost, Helmchen, Pfaltz and others have focused primarily on the direct allylation of malonates by prochiral electrophiles ... 

The direct allylation of radical precursors (e.g., alkyl hahdes, thioacyl derivatives) with allyltributylstannane in the presence of an initiator represents a well-established protocol for carbon-carbon bond formation [29,30]. This methodology provides a convenient means for introducing an allyl group to the anomeric carbon of carbohydrates [31]. hi their recent work on the preparation of building blocks for C-glycoside synthesis, Postema and coworkers... 

Yamamoto et al. [185] have recently described the direct allylation of various pronucleophiles catalyzed by Pd2(dba)3 (Scheme 4-47) these reactions are particularly unusual in that the organotin product formed is tributyltin hydride. The latter was not isolated but was observed iiT e product mixture by NMR. 

The excellent diastereoselection of all three of these substrate-directed allylation reactions is consistent with reaction occurring through Felkin transition states analogous to 39 (Fig. 11-6). These examples illustrate the excellent stereochemical control opportunities that exist in ( )-crotylation reactions of a-methyl chiral aldehydes, especially when the -position is branched (as in the (7s)-crotylation of 25 and 32, see above). 

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